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Dung-Tsa Chen, Ying-Lin Hsu, William J. Fulp, Domenico Coppola, Eric B. Haura, Timothy J. Yeatman, W. Douglas Cress, Prognostic and Predictive Value of a Malignancy-Risk Gene Signature in Early-Stage Non–Small Cell Lung Cancer, JNCI: Journal of the National Cancer Institute, Volume 103, Issue 24, 21 December 2011, Pages 1859–1870, https://doi.org/10.1093/jnci/djr420
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Abstract
The malignancy-risk gene signature is composed of numerous proliferative genes and has been applied to predict breast cancer risk. We hypothesized that the malignancy-risk gene signature has prognostic and predictive value for early-stage non–small cell lung cancer (NSCLC) patients.
The ability of the malignancy-risk gene signature to predict overall survival (OS) of early-stage NSCLC patients was tested using a large NSCLC microarray dataset from the Director’s Challenge Consortium (n = 442) and two independent NSCLC microarray datasets (n = 117 and 133, for the GSE13213 and GSE14814 datasets, respectively). An overall malignancy-risk score was generated by principal component analysis to determine the prognostic and predictive value of the signature. An interaction model was used to investigate a statistically significant interaction between adjuvant chemotherapy (ACT) and the gene signature. All statistical tests were two-sided.
The malignancy-risk gene signature was statistically significantly associated with OS (P < .001) of NSCLC patients. Validation with the two independent datasets demonstrated that the malignancy-risk score had prognostic and predictive values: Of patients who did not receive ACT, those with a low malignancy-risk score had increased OS compared with a high malignancy-risk score (P = .007 and .01 for the GSE13212 and GSE14814 datasets, respectively), indicating a prognostic value; and in the GSE14814 dataset, patients receiving ACT survived longer in the high malignancy-risk score group (P = .03), and a statistically significant interaction between ACT and the signature was observed (P = .02).
The malignancy-risk gene signature was associated with OS and was a prognostic and predictive indicator. The malignancy-risk gene signature could be useful to improve prediction of OS and to identify those NSCLC patients who will benefit from ACT.
